Variant 3-159995457-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_000882.4(IL12A):c.660G>A(p.Pro220=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,607,390 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

IL12A
NM_000882.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.40

Variant links:

Genes affected

IL12A (HGNC:5969): (interleukin 12A) This gene encodes a subunit of a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. The cytokine is a disulfide-linked heterodimer composed of the 35-kD subunit encoded by this gene, and a 40-kD subunit that is a member of the cytokine receptor family. This cytokine is required for the T-cell-independent induction of interferon (IFN)-gamma, and is important for the differentiation of both Th1 and Th2 cells. The responses of lymphocytes to this cytokine are mediated by the activator of transcription protein STAT4. Nitric oxide synthase 2A (NOS2A/NOS2) is found to be required for the signaling process of this cytokine in innate immunity. [provided by RefSeq, Jul 2008]

IL12A links:

IL12A-AS1 (HGNC:49094): (IL12A antisense RNA 1)

IL12A-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-159995457-G-A is Benign according to our data. Variant chr3-159995457-G-A is described in ClinVar as [Benign]. Clinvar id is 721071.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.4 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IL12A	NM_001397992.1 linkuse as main transcript	c.558G>A	p.Pro186=	synonymous_variant	7/7	ENST00000699704.1
IL12A	NM_000882.4 linkuse as main transcript	c.660G>A	p.Pro220=	synonymous_variant	7/7
IL12A-AS1	NR_108088.1 linkuse as main transcript	n.1085-1152C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12A	ENST00000699704.1 linkuse as main transcript	c.558G>A	p.Pro186=	synonymous_variant	7/7		NM_001397992.1	P1
IL12A-AS1	ENST00000497452.5 linkuse as main transcript	n.1085-1152C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

173

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00105

AC:

259

AN:

245692

Hom.:

AF XY:

0.00105

AC XY:

140

AN XY:

132844

show subpopulations

Gnomad AFR exome

AF:

0.000251

Gnomad AMR exome

AF:

0.00163

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000166

Gnomad SAS exome

AF:

0.000172

Gnomad FIN exome

AF:

0.00292

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.000846

GnomAD4 exome

AF:

0.00144

AC:

2089

AN:

1455126

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

981

AN XY:

723774

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.000154

Gnomad4 FIN exome

AF:

0.00289

Gnomad4 NFE exome

AF:

0.00154

Gnomad4 OTH exome

AF:

0.00175

GnomAD4 genome

AF:

0.00114

AC:

173

AN:

152264

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.00135

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.00117

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.6

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over